The goal of this project is to understand the underlying physiological mechanisms of different involuntary movement disorders. The tools we use include clinical neurophysiological methods such as electroencephalography, electromyography, and transcranial magnetic stimulation and neuroimaging with positron emission tomography and functional magnetic resonance imaging. Currently active projects in the Section include studies of tremor, tic, psychogenic movement disorders and paroxysmal movement disorders. New drugs are needed for treatment of essential tremor. Using tremor accelerometry and clinical tremor testing we have shown that 1-octanol, as a single dose, can be safely used (up to 64 mg/kg) and that it significantly reduces tremor in benign essential tremor. We have now started a study using octanol for longer periods of time. We are also planning to study the pharmacokinetics of octanol. We have been approaching the physiology of tics in many different ways. Using BOLD fMRI, we are examining what brain regions are activated during tics and tic imitations in patients with Tourette's syndrome and chronic tic disorder. Previous studies have used neuroimaging to show brain activation during tics as well as tic suppression. By studying both the patient's natural tics as well as the patient's voluntary imitation of the tic, we hope to find what brain areas may be activated in generating the urge to tic and the automatic movement that follows. We are also using blood flow PET to try to define the anatomy for tic generation. In this situation, we are using a sleep state for baseline so that we can have a state largely free of both tics and urge to tic. We have conducted a study looking at persons with paroxysmal kinesiogenic dystonia to characterize the condition better clinically. Simultaneously, there are attempts by an extramural collaborator to find the responsible mutated gene. We have begun to explore the pathophysiology of psychogenic movement disorders including tremor and myoclonus. We are doing EEG and neuroimaging studies trying to identify the parts of the brain responsible for movement initiation.